Infection Resistant Hemodialysis Access Graft v0.10 PROJECT SUMMARY Objective: The objective of this Phase I SBIR project is to validate a new synthetic vascular graft construction designed to reduce infection failures of arteriovenous (AV) grafts. Building upon a previously demonstrated approach for preventing venous-end stenosis (via suppression of perigraft fibrotic encapsulation), the new design includes features that enhance the effectiveness of the body?s natural immune defenses against device-associated infections. A successful outcome will verify this design?s capability to address both of the major causes of AV graft failure (stenosis and infection). Significance: Establishing and maintaining vascular access for hemodialysis patients is extremely challenging. As a result of slow maturation times and maturation failures in autogenous arteriovenous fistulas (the preferred vascular access option) and a reluctance to use synthetic AV grafts (the next safest alternative) due to infection concerns and poor patency, more than half of all first-year patients, and more than 20% longer term, are treated via ?last-resort? infection- prone catheters. There is a desperate need for an improved AV graft to reduce reliance on catheters. Innovation: Healionics? STARgraft AV+ is a new way to address the AV graft infection problem. Featuring a microporous sheath with tightly controlled pore geometry (30-m spherical pores interconnected by 12-m openings), placed over the exterior of a conventional ePTFE graft, the new device is designed to combat infection via multiple mechanisms: 1) Immune cell-accessible surface area within the pore space is maximized, concentrating favorably-activated protective macrophages. 2) The pore structure and surrounding tissue become permanently vascularized and fibrotic encapsulation is suppressed, enabling phagocytic immune cells to migrate freely. 3) Remarkably, the high concentration of immune cells and unimpeded cell migration within the protective sheath layer has been shown to provide a ?Halo Effect?, infusing the pore spaces of the inner ePTFE core layer with protective immune cells. This effect appears to further reduce infection vulnerability by accelerating fibrotic tissue repair within the holes of the graft wall after needle punctures. Approach: Performance of the new AV graft will be evaluated in an established sheep model, adapted to allow bacterial challenges via repeated mock dialysis sessions (i.e., cannulation with large needles). The specific aim is to demonstrate superior infection control (i.e., a reduced level of bacterial colonization) compared to conventional grafts. Impact: A new AV graft that reliably avoids stenosis and infection problems would provide a much-improved vascular access option and improved quality of life for a large segment of the dialysis patient population, especially by reducing hospitalizations and mortality due to catheter-related bloodstream infections. Full development would also have an enormous collateral economic benefit ? even a 10% reduction in access-related severe infections would save more than $1B annually to the health care system.